Chewing gum having sustained release of nicotine

ABSTRACT

The present invention relates to a chewing gum having a high Surface Area to Volume ratio (SAV ratio), wherein said chewing gum comprises a water insoluble gum base matrix, a water soluble bulk portion and nicotine, wherein the gum base matrix, nicotine and the bulk portion are mixed and extruded to form a final extruded chewing gum product having a SAV ratio above 0.7, and wherein sustained release of nicotine is facilitated by adding 0.1-10% of C8-C10 triglycerides by weight of the chewing gum.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/360,102, filed Jan. 27, 2012, entitled CHEWING GUM HAVING SUSTAINEDRELEASE OF NICOTINE, and published as US 2013-0011343, which claimspriority to and/or benefit of Danish Patent Application Serial No. PA2011 00516, filed Jul. 6, 2011. U.S. patent application Ser. No.13/360,102, US 2013-0011343 and PA 2011 00516 are herein incorporated byreference in their entirety.

TECHNICAL FIELD

The present invention relates to the field of chewing gum. In particularthe present invention relates to a chewing gum having sustained releaseof nicotine.

BACKGROUND

It is well known to use chewing gum comprising nicotine or complexes ofnicotine to provide a user with appropriate doses of nicotine.

Considerable effort has been put into formulating chewing gum that candeliver nicotine to a user in a way close to what is experienced by aperson when smoking a cigarette.

Different ways of incorporating the nicotine into the chewing gum bymixing or initial preparation of the nicotine have been disclosed in theprior art.

One of these prior art disclosures includes U.S. Pat. No. 5,488,962specifically dealing with the problem of simulating the cigarettesmoking with respect to the level of nicotine retention in the blood andsaliva. According to the disclosure, an initial peak of nicotine levelin the blood is obtained more similar to the corresponding absorption ofnicotine when smoking a cigarette. The levels reached after a certaintime corresponds to conventional nicotine-containing chewing gums.

A problem is, however, that a too high initial release may result in toomuch nicotine released, which may therefore cause a sense of burning inthe mouth of a user.

It is therefore an object of the present invention to obtain a nicotinechewing gum with a sustained release of nicotine as compared to priorart nicotine-containing chewing gums.

SUMMARY

The present invention relates to a chewing gum, wherein said chewing gumcomprises a water insoluble gum base matrix, a water soluble bulkportion and nicotine, wherein the gum base matrix, nicotine and the bulkportion are mixed and extruded to form a final extruded chewing gumproduct, and wherein sustained release of nicotine is facilitated byadding 0.1-10% of C8-C10 triglycerides by weight of the chewing gum.

According to some aspects of the present invention the addition ofC8-C10 triglycerides to a chewing gum has surprisingly been found toaffect the release of nicotine in chewing gum, preferably withcomparatively high Surface Area to Volume ratio (SAV ratio), in a waythat makes such chewing gum suitable for delivering nicotine inappropriate amounts to a person chewing a chewing gum according to thepresent invention.

It has been found by the present inventors that C8-C10 triglycerides inchewing gum, preferably with comparatively large surface areas, may bothstabilize the nicotine in the chewing gum and facilitate a sustainedrelease of the nicotine.

The phrase “sustained release” herein refers to a release of nicotinewhere the amount of nicotine released from the chewing gum over time, asthe chewing gum is chewed, is somewhat delayed when compared to priorart nicotine chewing gum. Prior art chewing gum typically delivers aninitial burst of nicotine and a relative high release of nicotine duringthe first few minutes of chewing. The sustained release of the inventivechewing gum implies that less nicotine is released during the firstminutes of chewing where after the release gradually increases.

The initial burst of nicotine may be desirable in some cases but alsohas serious drawbacks, such as the effect of “burning” described below.

Because of these surprising effects of stabilization and sustainment ofnicotine release further advantages are obtained according toembodiments of the invention.

Nicotine release from chewing gum with comparatively large surface areasis expected to be at least initially fast which may result in theunwanted effect of “burning”, an unpleasant taste and sensation in themouth. By adding efficient amounts of C8-C10 triglycerides to thechewing gum, this “burning” may be avoided. Thereby the quality andcustomer acceptance of such chewing gum may be greatly improved. The“burning” is primarily experienced during the first 5 minutes or so ofchewing and this initial burning may be markedly less in the inventivechewing gum when compared to the prior art.

Furthermore it has also been established by the present inventors that avery favorable soft initial chew is obtained as a consequence of addingC8-C10 triglycerides to the chewing gum. Prior art nicotine chewing gumoften may tend to possess a rather hard initial chew.

With respect to flavor, the taste intensity of the chewing gum accordingto the present invention compares well with the prior art. For othertextural properties such as elasticity, the inventive chewing gumresembles prior art nicotine chewing gum very well.

In an embodiment of the invention, the C8-C10 triglycerides have adegree of saturation of at least 80%, such as at least 95%.

A very favorable texture of the chewing gum is obtained by using C8-C10triglycerides having a high degree of saturation.

It has been found by the present inventors that an aspect relating tothe present invention is the stability of the C8-C10 triglycerides withrespect to e.g. oxidation.

According to an embodiment of the present invention, a relatively highdegree of saturation of the C8-C10 triglycerides is preferable becausethe risk of oxidation and taste off-notes is diminished.

Furthermore, the possible amount of problematic trans-fatty-acids addedto the chewing gum with the C8-C10 becomes insignificant when the C8-C10triglycerides have a high degree of saturation.

In an embodiment of the invention, the SAV ratio of the chewing gum isabove 0.7. In a further embodiment of the invention, the SAV ratio ofthe chewing gum is above 0.75, such as above 0.8.

Even though the chewing gum according to embodiments of the inventionmay have a comparatively large surface area and nicotine is vulnerabletowards e.g. oxidation, it has surprisingly been found that the C8-C10triglycerides added to the chewing gum stabilize the nicotine, wherebyboth an improved shelf life of the chewing gum is obtained and at thesame time, an efficient use of the comparatively expensive nicotine ispromoted.

In an embodiment of the invention, the SAV ratio of the chewing gum isbelow 3, such as below 1.

In an embodiment of the invention, the C8-C10 triglycerides compriseless than 1% unsaturated fatty acid triglycerides.

In an embodiment of the invention, the chewing gum comprises C8-C10triglycerides in an amount of above 0.3%, such as above 0.5%, above0.7%, above 0.9%, above 1.15%, or above 1.3% by weight of the chewinggum.

In an embodiment of the invention, the chewing gum comprises C8-C10triglycerides in an amount of below 9%, such as below 8%, below 7%,below 6%, below 5%, or below 4% by weight of the chewing gum.

According to embodiments of the invention, depending on, among otherfactors, the SAV ratio of the chewing gum and the exact gum basecomposition, effective amounts of C8-C10 triglycerides to obtain some orall of the abovementioned effects and advantages are added to thechewing gum.

In an embodiment of the invention, the chewing gum comprises C2-C6triglycerides in an amount of less than 1% by weight of the chewing gum,such as less than 0.5% or less than 0.3%.

A chewing gum with too large amounts of triglycerides of C6 or lower mayhave a too soft texture to give a pleasant chew feel. Furthermore, therelease of nicotine will be faster than typically desired.

In an embodiment of the invention, the chewing gum comprises less than1% by weight of the chewing gum of C12 or higher triglycerides added tothe chewing gum together with the bulk portion, that is, as separatecomponents outside the gum base, such as less than 0.5% or less than0.3%.

A chewing gum with too large amounts of triglycerides of C12 or higheradded as separate components outside the gum base may have a too hardtexture to give a pleasant chew feel.

In an embodiment of the invention, the chewing gum formulation has aweight in the range of 0.1 to 10 grams, preferably in the range of 0.5to 4 grams.

In an embodiment of the invention, the chewing gum has at least onedimension of less than 4 mm, such as less than 3 or 2 mm.

In an embodiment of the invention, the chewing gum comprises glycerin inan amount of between 0.001 and 2% by weight of the chewing gum, such asbetween 0.1 and 1.5% by weight.

In an embodiment of the invention, larger amounts of glycerin in thechewing gum tend to soften the chewing gum too much when combined witheffective amounts of C8-C10 triglycerides. Furthermore, destabilizationof nicotine may occur, if glycerin is present in the chewing gum inlarge amounts.

In some embodiments of the invention, comparatively small amounts ofglycerin are highly desirable and an excellent texture of the chewinggum is obtained.

In an embodiment of the invention, the chewing gum comprises flavor andwherein the release of the flavor from the chewing gum is less affectedby the addition of C8-C10 triglycerides than the release of nicotinefrom the chewing gum.

It has surprisingly been found by the present inventors that in anembodiment of the invention, the release of flavor from the chewing gumis less affected by the addition of C8-C10 triglycerides than therelease of nicotine from the chewing gum. In this way, a very effectivetaste-masking of the nicotine is established, providing a chewing gumwith an at least initially very pleasant taste, making such embodimentadvantageous when compared to prior art products.

In an embodiment of the invention, said triglycerides impart a soft chewof the chewing gum.

Tests have shown that the novel chewing gum formulations comprisingC8-C10 triglycerides may have a soft chew feel both initially andthroughout the chew process which often is preferred over the ratherhard chew feel of some prior art products. Although this is a morequalitative feature of some embodiments of the invention, the term “softchew” is meaningful to those skilled in the art.

In an embodiment of the invention, the C8-C10 triglycerides are added aspart of the chewing gum without being pre-mixed with chewing gumingredients before the addition to the chewing gum.

By keeping the C8-C10 triglycerides separate from other chewing gumingredients in the manufacturing process, an advantageous embodiment ofthe present invention has been obtained.

In an embodiment of the invention, the C8-C10 triglycerides are notadded as part of an encapsulation system.

In an embodiment of the invention, the C8-C10 triglycerides are notadded as part of the insoluble gum base matrix.

In an embodiment of the invention, the nicotine is added in the form ofnicotine polacrilex.

In an embodiment of the invention, the chewing gum comprises nicotine inan amount of 0.5-8 mg, preferably 1-5 mg, such as 2 mg or 4 mg.

The amount of nicotine in chewing gum according to embodiments of theinvention may be varied depending on the actual release profile and thepurpose of a particular chewing gum product. Because of the sustainedrelease from the inventive chewing gum, comparatively high loads ofnicotine may be possible without negatively affecting the taste of thechewing gum. Also, due to the efficient and sustained administration ofthe nicotine to the person chewing the gum, low loads of nicotine arepossible, while still providing nicotine in doses relieving such personfrom nicotine cravings.

In an embodiment of the invention, less than 1 mg nicotine, such as lessthan 0.7 mg or less than 0.5 mg, is released from the chewing gum withinthe first 5 minutes from initiation of a chewing process carried out invitro on a chewing machine in accordance with European Pharmacopeia 4th.ed. 2.9.25, with a phosphate buffer with a pH of 7.4.

By adjusting the amounts of C8-C10 triglycerides in the chewing gum, therelease of nicotine from the chewing gum may be influenced. Typically,the initial nicotine release from the chewing gum, when chewed, may belower than the nicotine release would be without any C8-C10 glyceridesadded.

In an embodiment of the invention, less than 1.5 mg nicotine, such asless than 1.1 mg or less than 0.6 mg, is released from the chewing gumwithin the first 10 minutes from initiation of a chewing process carriedout in vitro on a chewing machine in accordance with EuropeanPharmacopeia 4th. ed. 2.9.25, with a phosphate buffer with a pH of 7.4.

According to embodiments of the invention, a relatively slow andsustained release is obtained through the addition of C8-C10triglycerides to the chewing gum.

In an embodiment of the invention, less than 40% of the total nicotinecontent in the chewing gum, such as less than 28%, less than 20%, lessthan 15% or less than 10%, is released from the chewing gum within thefirst 5 minutes from initiation of a chewing process carried out invitro on a chewing machine in accordance with European Pharmacopeia 4th.ed. 2.9.25, with a phosphate buffer with a pH of 7.4.

In an embodiment of the invention, less than 50% of the total nicotinecontent in the chewing gum, such as less than 38%, less than 28%, lessthan 20% or less than 15%, is released from the chewing gum within thefirst 10 minutes from initiation of a chewing process carried out invitro on a chewing machine in accordance with European Pharmacopeia 4th.ed. 2.9.25, with a phosphate buffer with a pH of 7.4.

A nicotine chewing gum may typically be chewed for an extended period oftime, e.g. 30 minutes. It may therefore be advantageous to apply chewinggum with a sustained release of nicotine providing efficient doses ofnicotine throughout the chewing time. Different release profiles ofnicotine may be obtained from chewing gum according to embodiments ofthe invention.

In one preferred embodiment, the nicotine release of the chewing gumwhen chewed, is slow initially (the first about 5 minutes), increasesbetween about 5 and about 20 minutes and again slowing down after about20 minutes of chewing. It has been found by the present inventors thatthis particular type of sustained release has some distinct advantages,including the diminishing of the earlier described “burning” and a veryeffective nicotine dosage during the period in time with increasedrelease.

Another nicotine release profile that may be achieved with theapplication of C8-C10 triglycerides in a chewing gum according toanother preferred embodiment of the invention and being quite differentfrom typical prior art nicotine release profiles is a slow initialrelease (the first about 5 minutes), an increase between about 5 andabout 20 minutes and a further increase after about 20 minutes ofchewing.

An advantage of this type of sustained release may be that the user hasan incitement to continue chewing the gum, because the relief fromnicotine cravings becomes more efficient, the longer the chewing gum ischewed, due to the sustained and increasing release of nicotine. In thisway it may be possible to reduce the frequency of taking a new chewinggum, whereby the overall nicotine uptake of the person using thisparticular embodiment of the present invention may be reduced.

In an embodiment of the invention, less than 65% of the total nicotinecontent in the chewing gum, such as less than 50%, less than 40% or lessthan 30%, is released from the chewing gum within the first 15 minutesfrom initiation of a chewing process carried out in vitro on a chewingmachine in accordance with European Pharmacopeia 4th. ed. 2.9.25, with aphosphate buffer with a pH of 7.4.

In an embodiment of the invention, less than 25% of the total nicotinecontent in the chewing gum is released from the chewing gum within thefirst 15 minutes from initiation of a chewing process carried out invitro on a chewing machine in accordance with European Pharmacopeia 4th.ed. 2.9.25, with a phosphate buffer with a pH of 7.4.

In an embodiment of the invention, the gum base comprises

-   -   elastomer in the range of 5-40% by weight of the gum base,    -   natural resin in the range of 8-45% by weight of the gum base,        and    -   synthetic resin in the range of 5-50% by weight of the gum base.

The gum base composition may vary according to embodiments of theinvention.

In an embodiment of the invention, the chewing gum comprises gum base inan amount of 15 to 95% by weight of the chewing gum, preferably 20 to90% by weight, such as 30 to 80% by weight, 35 to 70% by weight or 40 to60% by weight.

The gum base content of the chewing gum may vary according toembodiments of the invention.

In an embodiment of the invention, the chewing gum comprises gum base inan amount of 100 mg to 5000 mg, preferably 200 mg to 3000 mg, morepreferably 300 mg to 2000 mg, such as 400 mg to 1500 mg or 600 mg to1200 mg.

In an embodiment of the invention, the chewing gum comprises naturalresins in an amount of 0.1 to 40%, preferably 1 to 30%, such as 3 to 25%or 5 to 20%, by weight of the chewing gum.

In an embodiment of the invention, the chewing gum comprises syntheticresins in an amount of 0.1 to 40%, preferably 1 to 30%, such as 3 to 25%or 5 to 20%, by weight of the chewing gum.

In an embodiment of the invention, the chewing gum comprises terpeneresins in an amount of 2 to 15% by weight of the chewing gum.

In some embodiments, the amount of terpene resins may influence therelease of nicotine.

In an embodiment of the invention, the chewing gum comprises elastomerin an amount of at least 2% by weight of the chewing gum formulation,preferably at least 4% by weight of the chewing gum.

In an embodiment of the invention, the chewing gum comprises elastomerin an amount of less than 35% by weight of the chewing gum, preferablyless than about 25% by weight of the chewing gum such as less than 20%,15% or 10% by weight of the chewing gum.

In an embodiment of the invention, the gum base matrix comprises fats inan amount of less than 15% by weight of the chewing gum or less than 10%by weight of the chewing gum.

Moreover, the invention relates to a chewing gum comprising a waterinsoluble gum base matrix and a water soluble bulk portion and nicotine,wherein the gum base matrix, nicotine and the bulk portion are mixed andextruded to form a final extruded chewing gum product, and whereinstability of nicotine is facilitated by adding less than 1.0%hydrophilic softeners by weight of the chewing gum and wherein sustainedrelease of nicotine is facilitated by adding 0.1-10% of C8-C10triglycerides by weight of said chewing gum.

By keeping the amount of hydrophilic softeners relatively low, anefficient utilization of the added nicotine has been obtained and achewing gum with more predictable nicotine dosage has been obtained

Moreover, the invention relates to a chewing gum comprising a waterinsoluble gum base matrix and a water soluble bulk portion and nicotine,wherein the gum base matrix, nicotine and the bulk portion are mixed andextruded to form a final extruded chewing gum product, and whereinsustained release of nicotine is facilitated by adding 0.1-10% of C8-C10triglycerides by weight of said chewing gum.

According to the present invention the addition of C8-C10 triglyceridesto a chewing gum has surprisingly been found to affect the release ofnicotine in chewing gum in a way that makes such chewing gum suitablefor delivering nicotine in appropriate amounts to a person chewing achewing gum according to the present invention.

It has been found by the present inventors that C8-C10 triglycerides mayboth stabilize the nicotine in the chewing gum and facilitate asustained release of the nicotine.

Because of these surprising effects of stabilization and sustainment ofnicotine release further advantages are obtained according toembodiments of the invention.

Nicotine release from chewing gum is expected to be at least initiallyfast which may result in the unwanted effect of “burning”, an unpleasanttaste and sensation in the mouth. By adding efficient amounts of C8-C10triglycerides to the chewing gum, this “burning” may be avoided. Therebythe quality and customer acceptance of such chewing gum may be greatlyimproved. The “burning” is primarily experienced during the first 5minutes or so of chewing and this initial burning may be markedly lessin the inventive chewing gum when compared to the prior art.

Furthermore it has also been established by the present inventors that avery favorable soft initial chew may be obtained as a consequence ofadding C8-C10 triglycerides to the chewing gum. Prior art Nicotinechewing gum often may tend to possess a rather hard initial chew.

With respect to flavor, the taste intensity of the chewing gum accordingto the present invention compares well with the prior art. For othertextural properties such as elasticity, the inventive chewing gumresembles prior art nicotine chewing gum well.

DETAILED DESCRIPTION

By the terms “gum base” and “gum base matrix” is meant the mainlywater-insoluble and hydrophobic gum base ingredients that are mixedtogether before the bulk portion of the chewing gum is added.

The term “bulk portion” intends to mean the mainly water-soluble andhydrophilic chewing gum ingredients that are mixed into the gum basematrix after it has been made.

The term “weight of the chewing gum” or similar wording meaning the sameis defined in the present context as weight of the chewing gum, notincluding the weight of an outer coating, such as a hard coating, softcoating, and the like.

By the phrase “texture” is meant a qualitative measure of thevisco-elastic properties of the chewing gum and of the overallmouth-feel experienced by the user during the chewing process. Thus theterm “texture” encompasses measurable quantities such as hardness andelasticity as well as more subjective parameters related to thechew-feel experienced by a user.

The phrase “hydrophobic” is used to describe the ability of a substanceto dissolve in or blend with apolar substances such as e.g. oils, waxesand hydrocarbon-based polymers.

The phrase hydrophilic is used to describe the ability of a substance todissolve in or blend with polar substances, such as e.g. water.

The term Surface Area to Volume ratio (SAV ratio) as used herein is adimensionless ratio defined as the total surface area (SA) of thechewing gum measured in mm² multiplied by 1 mm and divided by the volume(V) of the same chewing gum measured in mm³.

The SAV ratio is used to describe the exposure of the object to thesurroundings relative to the size of the object. Usually,nicotine-containing chewing gum has a comparatively low SAV ratio. Anessential reason for this is that nicotine is vulnerable to oxidationreactions and therefore, in the prior art, it has been advantageous tohave as much nicotine somewhat protected from the atmosphere inside thechewing gum as opposed to close to a surface. Because of the surprisingstabilization of nicotine when C8-C10 triglycerides are added to thechewing gum, the preferred format of the inventive chewing gum maysurprisingly be one with a comparatively high SAV ratio.

When in the present invention a chewing process is mentioned, suchchewing process is carried out in vitro on a chewing machine inaccordance with European Pharmacopeia 4th. ed. 2.9.25, with a phosphatebuffer with a pH of 7.4.

In some embodiments of the invention, a buffer is added, the bufferbeing selected from the group consisting of tris buffers, amino acidbuffers, carbonate, including monocarbonate, bicarbonate orsesquicarbonate, glycerinate, phosphate, glycerophosphate, acetate,glyconate or citrate of an alkali metal, such as potassium and sodium,e.g. trisodium and tripotassium citrate, or ammonium, and mixturesthereof.

When buffer is used, a preferred buffer is sodium bicarbonate. In someembodiments buffer is not part of the chewing gum. In some otherembodiments, buffer is part of the chewing gum. In some embodiments ofthe invention, the amount of buffer is 0.5 to 10% by weight of thechewing gum.

In some embodiments of the invention the buffer is selected from thegroup consisting of Acetic acid, Adipic acid, Citric acid, Fumaric acid,Glucono-δ-lactone, Gluconic acid, Lactic acid, Malic acid, Maleic acid,Tartaric acid, Succinic acid, Propionic acid, Ascorbic acid, Phosphoricacid, Sodium orthophosphate, Potassium orthophosphate, Calciumorthophosphate, Sodium diphosphate, Potassium diphosphate, Calciumdiphosphate, Pentasodium triphosphate, Pentapotassium triphosphate,Sodium polyphosphate, Potassium polyphosphate, Carbonic acid, Sodiumcarbonate, Sodium bicarbonate, Potassium carbonate, Calcium carbonate,Magnesium carbonate, Magnesium oxide, or any combination thereof.

The buffer may to some extent be microencapsulated or otherwise coatedas granules with polymers and/or lipids being less soluble in salivathan is the one or more buffering agents. Such microencapsulationcontrols the dissolution rate whereby is extended the time frame of thebuffering effect.

However, in a presently preferred embodiment an alkaline buffer ispreferred, such as sodium carbonate.

According to the invention a preferred amount of gum base matrix in thefinal chewing gum is above 30 percent by weight of the chewing gum core,such as above 35 percent by weight of the chewing gum core, such asabove 40 percent by weight of the chewing gum core, such as above 45percent by weight of the chewing gum core, such as about 40 percent byweight of the chewing gum core, such as about 47 percent by weight ofthe chewing gum core.

The formulation of gum bases can vary substantially depending on theparticular product to be prepared and on the desired masticatory andother sensory characteristics of the final product. However, typicalranges (% by weight) of the gum base components are: 5 to 80% by weightelastomeric compounds, 5 to 80% by weight natural and/or syntheticresins (elastomer plasticizers), 0 to 40% by weight waxes, 5 to 35% byweight softener other than waxes, 0 to 50% by weight filler, and 0 to 5%by weight of miscellaneous ingredients such as antioxidants, colourants,etc. The gum base may comprise about 5 to about 95 percent, by weight,of the chewing gum, more commonly the gum base comprises 10 to about 60percent, by weight, of the gum.

Elastomers provide the rubbery, cohesive nature to the gum, which variesdepending on this ingredient's chemical structure and how it may becompounded with other ingredients. Elastomers suitable for use in thegum base and gum of the present invention may include natural orsynthetic types.

Elastomer plasticizers vary the firmness of the gum base. Theirspecificity on elastomer inter-molecular chain interaction(plasticizing) along with their varying softening points cause varyingdegrees of finished gum firmness and compatibility when used in base.This may be important when one wants to provide more elastomeric chainexposure to the alkane chains of the waxes.

The elastomers (rubbers) employed in the gum base may vary dependingupon various factors such as the type of gum base desired, the textureof gum formulation desired and the other components used in theformulation to make the final chewing gum product. The elastomer may beany water-insoluble polymer known in the art, and includes those gumpolymers utilized for chewing gums and bubble gums. Illustrativeexamples of suitable polymers in gum bases include both natural andsynthetic elastomers. For example, those polymers which are suitable ingum bases include, without limitation, natural substances (of vegetableorigin) such as chicle gum, natural rubber, crown gum, nispero,rosidinha, jelutong, perillo, niger gutta, tunu, balata, guttapercha,lechi capsi, sorva, gutta kay, and the like, and mixtures thereof.Examples of synthetic elastomers include, without limitation,styrene-butadiene copolymers (SBR), polyisobutylene,isobutylene-isoprene copolymers, polyethylene, polyvinyl acetate and thelike, and mixtures thereof.

Natural resins may be used according to the invention and may be naturalrosin esters, often referred to as ester gums including as examplesglycerol esters of partially hydrogenated rosins, glycerol esters ofpolymerised rosins, glycerol esters of partially dimerized rosins,glycerol esters of tally oil rosins, pentaerythritol esters of partiallyhydrogenated rosins, methyl esters of rosins, partially hydrogenatedmethyl esters of rosins, pentaerythritol esters of rosins, syntheticresins such as terpene resins derived from alpha-pinene, beta-pinene,and/or d-limonene, and natural terpene resins.

In an embodiment of the invention, the resin comprises terpene resins,e.g. derived from alpha-pinene, beta-pinene, and/or d-limonene, naturalterpene resins, glycerol esters of gum rosins, tall oil rosins, woodrosins or other derivatives thereof such as glycerol esters of partiallyhydrogenated rosins, glycerol esters of polymerized rosins, glycerolesters of partially dimerised rosins, pentaerythritol esters ofpartially hydrogenated rosins, methyl esters of rosins, partiallyhydrogenated methyl esters of rosins or pentaerythritol esters of rosinsand combinations thereof.

In an embodiment of the invention, said chewing gum ingredients areselected from the group consisting of bulk sweeteners, flavors,dry-binders, tabletting aids, anti-caking agents, emulsifiers,antioxidants, enhancers, absorption enhancers, buffers, high intensitysweeteners, softeners, colors, or any combination thereof.

In an embodiment of the invention, said emulsifiers are selected fromthe group of cyclodextrins, polyoxyethylene castor oil derivatives,polyoxyethylene alkyl ethers, macrogol alkyl ethers, block copolymers ofethylene and propylene oxides, polyoxyethylene alkyl ethers,polyoxyethylene glycols, polyoxyethylene sorbitan fatty acid esters,polyoxyethylene (20) sorbitan monostearates, polyoxyethylene (20)sorbitan monooleates, polyoxyethylene stearates, sobitan esters,diacetyl tartaric ester of monoglycerides, lactylated monoglycerides, orany combination thereof.

In an embodiment of the invention, said chewing gum comprisesemulsifiers in an amount in the range of 0.1% to 25% by weight of saidchewing gum.

Petroleum waxes aid in the curing of the finished gum made from the gumbase as well as improve shelf life and texture. Wax crystal sizeinfluences the release of flavor. Those waxes high in iso-alkanes have asmaller crystal size than those waxes high in normal-alkanes, especiallythose with normal-alkanes of carbon numbers less than 30. The smallercrystal size allows slower release of flavor since there is morehindrance of the flavor's escape from this wax versus a wax havinglarger crystal sizes. The compatibility of gum bases made usingnormal-alkanic waxes is less when compared to gum bases made withiso-alkanic waxes.

Petroleum wax (refined paraffin and microcrystalline wax) and paraffinwax are composed of mainly straight-chained normal-alkanes and branchediso-alkanes. The ratio of normal-alkanes to iso-alkanes varies.

The normal-alkanic waxes typically have carbon chain lengths >C-18 butthe lengths are not predominantly longer than C-30. The branched andring structures are located near the end of the chain for those waxesthat are predominantly normal-alkanic. The viscosity of normal-alkanicwaxes is <10 mm2/s (at 100° C.) and the combined number averagemolecular weight is <600 g/mole.

The iso-alkanic waxes typically have carbon lengths that arepredominantly greater than C-30. The branched chains and ring structuresare located randomly along the carbon chain in those waxes that arepredominantly iso-alkanic. The viscosity of iso-alkanic waxes is greaterthan 10 mm2/s (at 100° C.) and the combined number average molecularweight is >600 g/mole. Synthetic waxes are produced by means that areatypical for petroleum wax production and are thus not consideredpetroleum wax. The synthetic waxes may include waxes containing branchedalkanes and copolymerized with monomers such as, but not limited topropylene, polyethylene, and Fischer Tropsch type waxes. Polyethylenewax is a synthetic wax containing alkane units of varying lengths havingattached thereto ethylene monomers.

Waxes and fats are conventionally used for the adjustment of the textureand for softening of the chewing gum base when preparing chewing gumbases. In connection with the present invention, any conventionally usedand suitable type of natural and synthetic wax and fat may be used, suchas for instance rice bran wax, polyethylene wax, petroleum wax (refinedparaffin and microcrystalline wax), sorbitan monostearate, tallow,propylene glycol, paraffin, beeswax, carnauba wax, candelilla wax, cocoabutter, degreased cocoa powder and any suitable oil or fat, as e.g.completely or partially hydrogenated vegetable oils or completely orpartially hydrogenated animal fats.

Antioxidants prolong shelf life and storage of gum base, finished gum ortheir respective components including fats and flavor oils.

Antioxidants suitable for use in gum base include butylatedhydroxyanisole (BHA), butylated hydroxytoluene (BHT), betacarotenes,tocopherols, acidulants such as Vitamin C, propyl gallate, othersynthetic and natural types or mixtures thereof. In an embodiment of theinvention, said nicotine is in a form selected from nicotine salts,nicotine free base, nicotine bound in a complex, or any combinationthereof.

In an embodiment of the invention, said complex comprises an ionexchange resin.

In an embodiment of the invention, said ion exchange resin is a weaklyacidic cation exchange resin.

According to an embodiment of the invention, a preferred example of aweakly acidic cation exchange resin is polacrilex.

In an embodiment of the invention, said complex comprises an adsorbent.

In an embodiment of the invention, said adsorbent is selected from thegroup consisting of finely divided silicic acid, amorphous silica,magnesium silicate, calcium silicate, kaolin, clays, crystallinealuminosilicates, macaloid bentonite, activated carbon, alumina,hydroxylapatite, microcrystalline cellulose, or any combination thereof.

In an embodiment of the invention, said nicotine salts are selected fromthe group comprising nicotine hydrochloride, nicotine dihydrochloride,nicotine monotartrate, nicotine bitartrate, nicotine sulfate, nicotinezinc chloride, nicotine salicylate, or any combination thereof.

In an embodiment of the invention, the chewing gum comprises sweeteners,such as bulk sweeteners, sugar sweeteners, sugar substitute sweeteners,artificial sweeteners, high-intensity sweeteners, or any combinationthereof.

Suitable bulk sweeteners include both sugar and non-sugar sweeteningcomponents. Bulk sweeteners typically constitute from about 5 to about95% by weight of the chewing gum, more typically about 20 to about 80%by weight such as 30 to 70% or 30 to 60% by weight of the gum.

Useful sugar sweeteners are saccharide-containing components commonlyknown in the chewing gum art including, but not limited to, sucrose,dextrose, maltose, dextrins, trehalose, D-tagatose, dried invert sugar,fructose, levulose, galactose, corn syrup solids, and the like, alone orin combination.

Sorbitol can be used as a non-sugar sweetener. Other useful non-sugarsweeteners include, but are not limited to, other sugar alcohols such asmannitol, xylitol, hydrogenated starch hydrolysates, maltitol, isomalt,erythritol, lactitol and the like, alone or in combination.

High intensity artificial sweetening agents can also be used alone or incombination with the above sweeteners. Preferred high intensitysweeteners include, but are not limited to sucralose, aspartame, saltsof acesulfame, alitame, saccharin and its salts, cyclamic acid and itssalts, glycyrrhizin, dihydrochalcones, thaumatin, monellin, steriosideand the like, alone or in combination. In order to provide longerlasting sweetness and flavor perception, it may be desirable toencapsulate or otherwise control the release of at least a portion ofthe artificial sweeteners. Techniques such as wet granulation, waxgranulation, spray drying, spray chilling, fluid bed coating,conservation, encapsulation in yeast cells and fiber extrusion may beused to achieve desired release characteristics. Encapsulation ofsweetening agents can also be provided using another chewing gumcomponent such as a resinous compound.

Usage level of the artificial sweetener will vary considerably and willdepend on factors such as potency of the sweetener, rate of release,desired sweetness of the product, level and type of flavor used and costconsiderations. Thus, the active level of artificial sweetener may varyfrom about 0.001 to about 8% by weight (preferably from about 0.02 toabout 8% by weight). When carriers used for encapsulation are included,the usage level of the encapsulated sweetener will be proportionatelyhigher. Combinations of sugar and/or non-sugar sweeteners may be used inthe chewing gum.

A chewing gum and/or gum base may, if desired, include one or morefillers/texturisers including as examples, magnesium and calciumcarbonate, sodium sulphate, ground limestone, silicate compounds such asmagnesium and aluminum silicate, kaolin and clay, aluminum oxide,silicium oxide, talc, titanium oxide, mono-, di- and tri-calciumphosphates, cellulose polymers, such as wood, and combinations thereof.

A number of chewing gum components well known within the art may beapplied within the scope of the present invention. Such componentscomprise but are not limited to waxes, fats, softeners, fillers,flavors, anti-oxidants, emulsifiers, colouring agents, binding agentsand acidulants

According to embodiments of the invention, the C8 triglycerides comprisetriglycerides of caprylic acid and/or the C10 triglycerides comprisetriglycerides of capric acid. According to embodiments of the invention,the chewing gum is a stick chewing gum.

In an embodiment of the invention, the chewing gum is provided with anouter coating selected from the group consisting of hard coating, softcoating and edible film-coating or any combination thereof.

The following non-limiting examples illustrate different variations ofthe present invention. The examples are meant for indicating theinventive concept; hence the mentioned examples should not be understoodas exhaustive for the present invention.

EXAMPLES Example 1 Preparation of Gum Base

A gum base is prepared, which comprises the following ingredients.

Ingredients % by weight Elastomer 10 Natural resin 28 Synthetic resin 22Fat/wax/emulsifiers 23 Fillers 17

It should be emphasized that several other gum base compositions may beapplied within the scope of the invention.

The elastomer and filler are added to a mixing kettle provided withmixing means like e.g. horizontally placed Z-shaped arms. The kettle hasbeen preheated for 15 minutes to a temperature of about 120° C. Therubber is sheared and grinded with mechanical action in the kettle.

Resin is slowly added to the elastomer and filler until the mixturebecomes homogeneous. The remaining resin is then added to the kettle andmixed for 10-20 minutes. The softening ingredients are added and mixedfor 20-40 minutes until the whole mixture becomes homogeneous.

The mixture is then discharged into the pan and allowed to cool to roomtemperature from the discharged temperature of 120° C.

Example 2 Preparation of Nicotine-Containing Chewing Gum

Chewing gum is prepared by use of the gum base in example 1 andaccording to a conventional mechanical mixing procedure during moderateuse of heating as described below.

CG1 CG2 CG3 CG4 CG5 Gum base 43.4% 43.4% 43.4% 43.4% 43.4% Filler 14.6%14.6% 14.6% 14.6% 14.6% Nicotine Polacrilex Nicotine  0.2%  0.2%  0.2% 0.2%  0.2% Ion exchange resin  0.8%  0.8%  0.8%  0.8%  0.8% Bufferagents Sodium hydrogen  1.0%  1.0%  1.0%  1.0%  1.0% carbonate Sodiumcarbonate  2.0%  2.0%  2.0%  2.0%  2.0% C8  0.0%  1.3%  2.6%  5.2%  7.8%C10  0.0%  0.7%  1.4%  2.8%  4.2% Sorbitol powder 34.6% 31.4% 30.6%26.6% 22.6% Glycerin  0.0%  1.2%  0.0%  0.0%  0.0% Intense sweetener 0.4%  0.4%  0.4%  0.4%  0.4% Flavor  3.0%  3.0%  3.0%  3.0%  3.0%

Gum base and filler are mixed batch-wise in a mixing kettle providedwith mixing means like e.g. horizontally placed Z-shaped arms. Thekettle has been preheated to a temperature of up to approximately 50° C.

When the content is homogenous the other ingredient is added accordingto a specified time schedule. Nicotine is added in the first half of themixing process and can be added as pure nicotine, as a nicotine salt orbound to an ion exchange resin, e.g. Amberlite IRP 64.

Finally, after mixing, chewing gums are formed through extrusion androlling into chewing gum sticks.

Alternatively, the mixing step may be performed continuously in aconventional extruder process, partly or fully replacing the mixinginvolving the Z-blade mixer.

The pieces may be formulated with 0.1-8 mg of nicotine per piece,preferably 2 or 4 mg. The pieces evaluated below comprise 2 mg nicotine.

Example 3 Evaluation of Nicotine Release of CG1-CG4

Samples were evaluated by a test panel of 10 persons. The perceptualrelease is evaluated with respect to taste of the released nicotine.Each person could give a value between 0 and 10 and the sums of thesevalues are presented in table 1. The sensory analyses were in generalcarried out in line with ISO 4121-2003.

TABLE 1 Perceptual nicotine release, sums of 10 test persons values. Thetime given is from initiation of a chewing process. Amount of C8 and C10perceptual release % by weight 5 min 10 min 20 min 30 min CG1 0 42 58 7585 CG2 2 12 20 41 80 CG3 4 10 19 48 79 CG4 8 6 11 37 74

The nicotine release was increasingly sustained as the amount of C8 andC10 increased. As such, the amount of C8 and C10 may be used to adjustthe release profile of nicotine according to what is desired.

Example 4 Evaluation of Softness of CG1-CG5

A test panel of 10 persons was used. The softness is characterizedthrough a sensory evaluation. The reference evaluation of softness isreferred to as A=hard, B=medium, C=soft, D=too soft. The values givenfrom the test persons were collected and united into one averageevaluation, which are presented in table 2.

TABLE 2 Sensory evaluation of the softness of chewing gums CG1-CG5. Thetime given is from initiation of a chewing process. Amount of C8 and C10Evaluation of softness % by weight 2 min 4 min 6 min 8 min CG1 0 A A B BCG2 2 B B C C CG3 4 C C C C CG4 8 C C C D CG5 12 C C D D

The chewing gums turned softer as the amount of C8 and C10 increased.For a total amount of 12%, the chewing gum turned too soft over time.For a total amount of 8%, the chewing gum was very close to turningunpleasantly soft for chewing.

Example 5 Evaluation of Nicotine Release

The nicotine release was measured in vitro on two chewing gums CG6 andCG7 according to embodiments of the present invention with a total of 2%and 4%, respectively, of C8 and C10 as compared to a prior art chewinggum without any C8 and C10.

The measurements were carried out according to the procedure set forthin the Ph. Eur. 6^(th) ed. 2.9.25, at pH=7.4, a chewing rate of 60 chewper minute, and with the temperature of the medium at 37° C.

The nicotine content of the samples before and after chewing wasanalyzed according to standard HPLC-techniques.

TABLE 3 Nicotine release. The time given is from initiation of a chewingprocess as described. Amount of C8 and C10 Nicotine release (% AC(Actual Content)) % by weight 5 min 10 min 20 min 30 min Prior art CG 058 75 87 92 CG6 2 18 35 58 80 CG7 4 4 8 32 76

Example 6 Evaluation of Nicotine Release Versus Flavor Release for CG7

The nicotine release and the flavor release of CG7 and Prior art CG weremeasured. All values are given as percent by weight of total amount ofthe ingredient in question. The flavor in this specific measurement waspeppermint.

The measurements were carried out according to the procedure set forthin the Ph. Eur. 6^(th) ed. 2.9.25, at pH=7.4, a chewing rate of 60 chewper minute, and with the temperature of the medium at 37° C.

TABLE 4 Nicotine release compared to flavor release. The time given isfrom initiation of a chewing process as described. Amount of C8 and C10% by weight 5 min 10 min 20 min 30 min Nicotine release (% AC (ActualContent)) Prior art CG 0 58 75 87 92 CG7 4 4 8 32 76 Flavor release (%AC (Actual Content)) Prior art CG 0 28 36 43 47 CG7 4 20 28 34 39

For the prior art CG, it is seen that the release of nicotine and flavoris more or less synchronized. However, when a total amount of 4% of C8and C10 is present in the chewing gum, CG7, the flavor release is onlyslightly sustained, whereas the nicotine release is highly sustained.

Although the release data given above also depend on e.g. the gum basecomposition, a general trend confirming the surprising differentiatingeffects of C8 and C10 triglycerides between release of flavor andnicotine has been observed.

Example 7 Evaluation of Softness when Using Various Triglycerides

Chewing gum samples were prepared according to embodiments of thepresent invention with 4% triglyceride added as a separate component.The triglycerides used were of varying fatty acid chain length (denotedby the number of C atoms in the fatty acid employed).

A test panel of 10 persons was used. The softness is characterizedthrough a sensory evaluation. The values given from the test personswere collected and united into one average evaluation, which arepresented in table 5.

TABLE 5 Sensory evaluation of the softness of chewing gums Amount (% byweight) Evaluation of C2 C6 C8 C10 C12 C14 softness over time CG10 4 0 00 0 0 Too soft, unpleasant to chew CG11 0 4 0 0 0 0 Too soft, unpleasantto chew CG12 0 0 4 0 0 0 Excellent softness CG13 0 0 0 4 0 0 Excellentsoftness CG14 0 0 0 0 4 0 Too hard, unpleasant to chew CG15 0 0 0 0 0 4Too hard, unpleasant to chew CG16 0 0.4 2.0 1.6 0 0 Slightly soft butpleasant to chew CG17 0 0 1.8 1.9 0.2 0.1 Slightly hard but pleasant tochew

It is clearly seen that C8 and C10 are the two highly preferabletriglycerides. For triglycerides derived from shorter acids, the chewinggum turns too soft and for triglycerides derived from longer acids, thechewing gum turns too hard. However, it is seen that smaller amounts ofsmaller or larger triglycerides may be present while still maintainingacceptable texture.

Example 8 Evaluation of Burning from Nicotine Release

Samples were evaluated by a test panel of 10 persons. The burningsensation was given an intensity value from 0 (no burning) to 6 (highburning).The values given from the test persons were collected andunited into one average evaluation, which are presented in table 6. Thesensory analyses were in general carried out in line with ISO 4121-2003.

TABLE 6 Burning sensation, average of 10 test persons values. The timegiven is from initiation of a chewing process. Amount of C8 and C10Burning sensation over time (seconds) % by weight 15 70 130 250 310 490550 CG20 0 1.4 2.6 3.6 4.0 3.9 2.7 2.3 CG21 Between 2 and 4 1.2 2.1 2.62.5 2.7 2.8 2.8

The nicotine release was increasingly sustained as the amount of C8 andC10 increased. As such, the amount of C8 and C10 may be used to adjustthe release profile of nicotine according to what is desired.

Example 9 Further Measurements

Further measurements were carried out with further chewing gums withvarying contents of nicotine, elastomers, resins and buffer. In generalthese showed advantageous properties related to using C8 and C10triglycerides when desiring a sustained release of nicotine as comparedto conventional chewing gum.

What is claimed is:
 1. Chewing gum having a high Surface Area to Volume ratio (SAV ratio), wherein said chewing gum comprises: a water insoluble gum base matrix, a water soluble bulk portion and nicotine, wherein the gum base matrix, nicotine and the bulk portion are mixed and extruded to form a final extruded chewing gum product having a SAV ratio above 0.7, and wherein sustained release of nicotine is facilitated by adding 0.1-10% of C8-C10 triglycerides by weight of the chewing gum, whereby less than 40% of the total nicotine content in the chewing gum is released from the chewing gum within the first 5 minutes from initiation of a chewing process carried out in vitro on a chewing machine in accordance with European Pharmacopeia 4th. ed. 2.9.25, with a phosphate buffer with a pH of 7.4.
 2. Chewing gum according to claim 1, wherein the gum base comprises: elastomer in the range of 5-40% by weight of the gum base; natural resin in the range of 8-45% by weight of the gum base; and synthetic resin in the range of 5-50% by weight of the gum base.
 3. Chewing gum according to claim 1, wherein the C8-C10 triglycerides have a degree of saturation of at least 80%.
 4. Chewing gum according to claim 1, wherein the chewing gum comprises glycerin in an amount of between 0.001 and 2% by weight of the chewing gum.
 5. Chewing gum according to claim 1, wherein the chewing gum comprises nicotine in an amount of 0.5-8 mg.
 6. Chewing gum according to claim 1, wherein the nicotine is added in the form of nicotine polacrilex.
 7. Chewing gum comprising a water insoluble gum base matrix and a water soluble bulk portion and nicotine, wherein the gum base matrix, nicotine and the bulk portion are mixed and extruded to form a final extruded chewing gum product, and wherein stability of nicotine is facilitated by adding less than 1.0% hydrophilic softeners by weight of the chewing gum and wherein sustained release of nicotine is facilitated by adding 0.1-10% of C8-C10 triglycerides by weight of said chewing gum whereby less than 40% of the total nicotine content in the chewing gum is released from the chewing gum within the first 5 minutes from initiation of a chewing process carried out in vitro on a chewing machine in accordance with European Pharmacopeia 4th. ed. 2.9.25, with a phosphate buffer with a pH of 7.4.
 8. Chewing gum according to claim 7, wherein the gum base comprises: elastomer in the range of 5-40% by weight of the gum base; natural resin in the range of 8-45% by weight of the gum base; and synthetic resin in the range of 5-50% by weight of the gum base.
 9. Chewing gum according to claim 7, wherein the chewing gum comprises nicotine in an amount of 0.5-8 mg.
 10. Chewing gum according to claim 7, wherein the nicotine is added in the form of nicotine polacrilex.
 11. Chewing gum having a high Surface Area to Volume ratio (SAV ratio), wherein said chewing gum comprises: a water insoluble gum base matrix, a water soluble bulk portion and nicotine, wherein the gum base matrix, nicotine and the bulk portion are mixed and extruded to form a final extruded chewing gum product having a SAV ratio above 0.7, and wherein sustained release of nicotine is facilitated by adding 0.1-10% of C8-C10 triglycerides by weight of the chewing gum, whereby less than 65% of the total nicotine content in the chewing gum is released from the chewing gum within the first 15 minutes from initiation of a chewing process carried out in vitro on a chewing machine in accordance with European Pharmacopeia 4th. ed. 2.9.25, with a phosphate buffer with a pH of 7.4.
 12. Chewing gum according to claim 11, wherein the gum base comprises: elastomer in the range of 5-40% by weight of the gum base; natural resin in the range of 8-45% by weight of the gum base; and synthetic resin in the range of 5-50% by weight of the gum base.
 13. Chewing gum according to claim 11, wherein the chewing gum comprises glycerin in an amount of between 0.001 and 2% by weight of the chewing gum.
 14. Chewing gum comprising a water insoluble gum base matrix and a water soluble bulk portion and nicotine, wherein the gum base matrix, nicotine and the bulk portion are mixed and extruded to form a final extruded chewing gum product, and wherein stability of nicotine is facilitated by adding less than 1.0% hydrophilic softeners by weight of the chewing gum and wherein sustained release of nicotine is facilitated by adding 0.1-10% of C8-C10 triglycerides by weight of said chewing gum whereby less than 65% of the total nicotine content in the chewing gum is released from the chewing gum within the first 15 minutes from initiation of a chewing process carried out in vitro on a chewing machine in accordance with European Pharmacopeia 4th. ed. 2.9.25, with a phosphate buffer with a pH of 7.4.
 15. Chewing gum according to claim 14, wherein the gum base comprises: elastomer in the range of 5-40% by weight of the gum base; natural resin in the range of 8-45% by weight of the gum base; and synthetic resin in the range of 5-50% by weight of the gum base.
 16. Chewing gum according to claim 14, wherein the chewing gum comprises nicotine in an amount of 0.5-8 mg.
 17. Chewing gum according to claim 14, wherein the nicotine is added in the form of nicotine polacrilex.
 18. Chewing gum according to claim 11, wherein the chewing gum comprises nicotine in an amount of 0.5-8 mg.
 19. Chewing gum according to claim 11, wherein the nicotine is added in the form of nicotine polacrilex. 